α-MSH对EGTA发热的作用

目的：观察α－ＭＳＨ对ＥＧＴＡ发热反应的作用及其可能机制。方法：建立ＥＧＴＡ发热模型；在离体条件下，应用Ｆｕｒａ－２荧光指示剂测定细胞内Ｃａ２＋浓度（［Ｃａ２＋］ｉ）；体外培养下丘脑神经细胞。结果：α－ＭＳＨ能明显抑制ＥＧＴＡ性发热反应（Ｐ＜０．０１）；ＥＧＴＡ可以降低下丘脑神经细胞［Ｃａ２＋］ｉ水平（Ｐ＜０．０１），但α－ＭＳＨ不影响正常下丘脑神经细胞［Ｃａ２＋］ｉ及ＥＧＴＡ对下丘脑神经细胞［Ｃａ２＋］ｉ的作用（Ｐ＞０．０５）；ＥＧＴＡ可刺激体外培养的下丘脑神经细胞释放ＣＲＨ（Ｐ＜０．０５），而α－ＭＳＨ能抑制ＥＧＴＡ的这种作用（Ｐ＜０．０５）。结论：α－ＭＳＨ抑制中枢发热介质ＣＲＨ的产生可能是降低ＥＧＴＡ发热反应的主要机制之一；中枢ＣＲＨ的产生和释放增加可能是ＥＧＴＡ性发热的一个重要因素。     

家兔EGTA性发热时脑腹中隔区AVP含量的变化

本研究采用新西兰家兔４８只，随机分成４组，分别观察向侧脑室灌注ＥＧＴＡ、ＥＧＴＡ＋ＣａＣｌ＿２或ＣａＣｌ＿２对体温和脑腹中隔区ＡＶＰ含量的影响。结果表明，侧脑室灌注ＥＧＴＡ，不仅引起结肠温度明显上升（Ｐ＜０．００１）．还引起腹中隔区ＡＶＰ含量明显降低（Ｐ＜０．０５）；灌注ＥＧＴＡ后立即灌注ＣａＣｌ＿２，抑制了结肠温度的升高并逆转了腹中隔ＡＶＰ含量的降低。体温反应指数与腹中隔区ＡＶＰ含量呈显著负相关（ｒ＝－０．８３７４，Ｐ＜０．０１）；单独灌注ＣａＣｌ＿２引起结肠温度下降和腹中隔ＡＶＰ含量明显增加（Ｐ＜０．０１），提示ＡＴＰ可能参与ＥＧＴＡ性发热的中枢调节机制，中枢Ｃａ￣（２＋）浓度或Ｎａ￣＋／Ｃａ￣（２＋）比值变化可能是调控发热时腹中隔区ＡＶＰ释放的一个重要因素。     

尼可地尔降低血管平滑肌细胞内ATP诱导的游离钙浓度

目的：探讨尼可地尔对血管平滑肌细胞内游离钙（［Ｃａ２＋］ｉ）的影响及机理。方法：培养的兔主动脉平滑肌细胞加入Ｆｕｒａ－２ＡＭ２５μｍｏｌ／Ｌ,在３７℃下孵育５０ｍｉｎ,［Ｃａ２＋］ｉ用荧光分光光度计检测。结果：ＡＴＰ（０１ｍｍｏｌ／Ｌ）诱导的［Ｃａ２＋］ｉ峰相和持续相增加可被尼可地尔抑制,且呈剂量依赖性,尼可地尔（１０μｍｏｌ／Ｌ）的抑制作用可被优降糖（１０μｍｏｌ／Ｌ）完全阻断（峰相：５３０±３１ｖｓ５４４±４１ｎｍｏｌ／Ｌ,持续相：３７０±１９ｖｓ３８１±１１ｎｍｏｌ／Ｌ,Ｐ＞００５）;在无钙溶液中,先给尼可地尔能显著抑制ＡＴＰ诱导的［Ｃａ２＋］ｉ峰相增加。结论：尼可地尔抑制ＡＴＰ诱导的［Ｃａ２＋］ｉ增加,可能与减少细胞外钙内流及细胞内钙释放有关。     

内皮素对成年鼠离体心室肌细胞内游离钙浓度的影响及机制

目的和方法：采用分离的Ｓｐｒａｇｕｅ－Ｄａｗｌｅｙ大鼠心室肌细胞,以Ｆｕｒａ－２／ＡＭ荧光指示剂负载,检测心肌细胞内游离钙浓度（［Ｃａ２＋］ｉ）变化,探讨内皮素－１（ＥＴ－１）对［Ｃａ２＋］ｉ的作用及其机制。结果：ＥＴ－１（１×１０－７ｍｏｌ／Ｌ）引起［Ｃａ２＋］ｉ升高分两个时相：快速相和持续相,可被ＥＴＡ的特异性受体阻断剂ＢＱ１２３（２×１０－６ｍｏｌ／Ｌ）所阻断。移去细胞外液钙以及用百日咳毒素（２００ｎｇ／ｍＬ）处理１０ｈ后,ＥＴ－１仍引起快速相,但持续相消失。Ｒｙａｎｏｄｉｎｅ（４μｍｏｌ／Ｌ）和异搏定（２×１０－５ｍｏｌ／Ｌ）对ＥＴ－１诱导［Ｃａ２＋］ｉ升高的作用无显著影响。结论：ＥＴ－１升高［Ｃａ２＋］ｉ是通过ＥＴＡ受体介导;快速相［Ｃａ２＋］ｉ升高主要由胞内Ｒｙａｎｏｄｉｎｅ不敏感的钙池释放造成,与百日咳毒素敏感的Ｇ蛋白无关;持续相［Ｃａ２＋］ｉ升高主要由胞外Ｃａ２＋内流引起,不是通过电压依赖性Ｌ－型钙通道介导,与百日咳毒素敏感的Ｇ蛋白有关     

下丘脑[Ca^2＋]i,cAMP在家兔EGTA性发热机制中的作用

用６０只新西兰兔分两部分进行实验。（１）用１２只制备下丘脑细胞悬液，在离体条件下，应用Ｆｕｒａ－２荧光指示剂测定细胞内Ｃａ＾２＋浓度（Ｃａ＾２＋］ｉ）。结果表明，用ＥＧＴＡ络合神经细胞外Ｃａ＾２＋而降低细胞外Ｃａ＾２＋浓度时，下丘脑神经细胞（［Ｃａ＾２＋］ｉ）明显降低（Ｐ＞０．０１）；相反，增加细胞外Ｃａ＾２＋浓度，则［Ｃａ＾２＋］ｉ明显增高（Ｐ＞０．０１）。（２）用４８只家兔分４组，分别向侧脑室     

α—MSH对家兔ET性发热反应及脑腹中隔区AVP含量的影响

目的：研究脑腹中隔区精氨酸加压素（ＡＶＰ）在α－黑素细胞刺激素（αＭＳＨ）解热机制中的作用。方法：建立家兔ＥＴ性发热模型，观察侧脑室注射α－ＭＳＨ对家兔ＥＴ性发热反应及脑腹中隔区ＡＶＰ含量的影响。结果：（１）静脉注射ＥＴ（０３μｇ／ｋｇ）引起家兔明显的发热反应（Ｐ＜０００１），并增加脑腹中隔ＡＶＰ含量（Ｐ＜００５）；（２）静脉注射ＥＴ（０３μｇ／ｋｇ）３０ｍｉｎ后，侧脑室注射α－ＭＳＨ（２００ｎｇ／只），能明显抑制家兔发热反应，同时脑腹中隔区ＡＶＰ含量进一步显著增高（Ｐ＜０００１）；（３）侧脑室注射α－ＭＳＨ（２００ｎｇ／只）并不影响家兔正常体温，但增加脑腹中隔区ＡＶＰ含量（Ｐ＜００５）。结论：α－ＭＳＨ的解热作用可能部分是通过腹中隔ＡＶＰ增多来实现的，αＭＳＨ可能是引起发热时脑腹中隔区ＡＶＰ含量增加的一个重要因素。     

去甲肾上腺素对大鼠腹腔巨噬细胞内IP_3、［Ca~（2＋）］_i和Ia抗原表达

本文应用细胞膜放射标记和离子交换层析法测定巨噬细胞（ＭФ）内肌醇－１，４，５－三磷酸（ＩＰ３）、用Ｃａ￣（２＋）指示剂的分光光谱法测定ＭФ内Ｃａ￣（２＋）浓度（［Ｃａ￣（２＋）］）、用ＡＰＡＡＰ桥联酶标法检测ＭФ表面Ｉａ抗原的表达，研究去甲肾上腺素（ＮＥ）对大鼠腹腔的ＭФ内ＩＰ３、［Ｃａ￣（２＋）］ｉ和ＭФ表面ｌａ抗原表达的影响。结果显示ＮＥ（１０￣（－８）ｍｏｌ／Ｌ）可显著增高ＭФ中ＩＰ＿３含量（４４２±２２ｃｐｍ／１０￣６ｃｅｌｌｓ，对照组１０２±８ｃｐｍ／１０￣６ｃｅｌｌｓ，Ｐ＜０．０１）；ＮＥ可使ＭФ内［Ｃａ￣（２＋）］ｉ显著增高（３２２±７８ｎｍｏｌ／Ｌ，对照组９７±１７ｎｍｏｌ／Ｌ，Ｐ＜０．０１）；ＮＥ可显著增高ＭФ表面Ｉ－Ａ、Ｉ－Ｅ抗原的表达（６４±８％、５８±６％，对照组５０±３％，４４±４％，Ｐ＜０．０１）。提示神经递质ＮＥ促进ＭФ表面Ｉａ抗原表达的作用可能是通过第二信使ＩＰ＿３和Ｃａ￣（２＋）介导的。     

钙离子与牛磺酸两者跨心肌细胞膜内流的相互影响

目的和方法：取新生ＳＤ大鼠心室肌制备培养搏动心肌细胞，采用放射性同位素４５Ｃａ２＋及３Ｈ－牛磺酸示踪技术，观察钙离子与牛磺酸跨心肌细胞膜内流的相互影响。结果：（１）牛磺酸内流在低胞外Ｃａ２＋浓度（［Ｃａ２＋］ｏ，０．５ｍｍｏｌ／Ｌ）和高［Ｃａ２＋］ｏ（４０ｍｍｏｌ／Ｌ）均比正常［Ｃａ２＋］ｏ（１５ｍｍｏｌ／Ｌ）和高［Ｃａ２＋］ｏ（４０ｍｍｏｌ／Ｌ）时增加，尤以低［Ｃａ２＋］。时明显；异搏定（１０μｍｏｌ／Ｌ）能促进牛磺酸的内流；（２）１０～２０ｍｍｏｌ／Ｌ牛磺酸对不同［Ｃａ２＋］。（０５、１５和４０ｍｍｏｌ／Ｌ）下的Ｃａ２＋内流均有抑制作用，而１ｍｍｏｌ／Ｌ牛磺酸只抑制高［Ｃａ２＋］ｏ时Ｃａ２＋内流，对低［Ｃａ２＋］ｏ和正常［Ｃａ２＋］ｏ时Ｃａ２＋内流无明显作用；１～２０ｍｍｏｌ／Ｌβ－丙氨酸对Ｃａ２＋内流无明显影响。结论：胞外Ｃａ２＋浓度的变化可直接影响牛磺酸内流，而牛磺酸能抑制Ｃａ２＋的内流，两者相互影响，从而发挥牛碘酸调节细胞内Ｃａ２＋浓度的作用     

SRBC膜提取物对猪PBMNC第二信使的影响

胰酶水解绵羊红细胞（ＳＲＢＣ）释放膜表面活性蛋白组分Ⅲ（ＴＲＦ－Ⅲ），单独作用可使猪外周血单个核细胞（ＰＢＭＮＣ）胞内ｃＡＭＰ水平升高，以１００μｇ／ｍｌ浓度刺激达最高峰，由对照组０．９４±０．１４ｐｍｏｌ／Ｌ升高到２．７５±０．２５ｐｍｏｌ／Ｌ（Ｐ＜０．０１）。如果ＰＢＭＮＣ事先与腺苷酸环化酶（ＡＣａｓｅ）抑制剂ＬｉC１孵育后再以ＴＲＦ－Ⅲ或ＰＡＨ刺激。ｃＡＭＰ增高受到抑制（Ｐ＜０．０１）；而ＥＤＴＡ－２Ｎａ（一种磷酸二酯酶ＰＤＥ抑制剂）对此ｃＡＭＰ升高无影响。结果提示，此ｃＡＭＰ升高主要是通过活化ＡＣａｓｅ水解ＡＴＰ生成ｃＡＭＰ，而不像是抑制ＰＤＥ减少ｃＡＭＰ降解引起的。ＴＲＦ－Ⅲ诱导猪ＰＢＭＮＣ胞内Ｃａ~(２＋)浓度升高，以１００μｇ／ｍｌ刺激２分钟升高最多，由对照组的２４２±７ｎｍｏｌ／Ｌ升高到３２３±１５ｎｍｏｌ／Ｌ（Ｐ＜０．０１）。以ＥＧ－ＴＡ除去胞外Ｃａ~(２＋)再以ＴＲＦ－Ⅲ或ＰＡＨ刺激，仅观察到小范围［Ｃａ~(２＋)］ｉ升高。看来这一过程包括了刺激胞内Ｃａ~(２＋)释放和胞外Ｃａ~(２＋)内流两种方式。以上结果证明，ＴＲＦ－Ⅲ对淋巴细胞功能影响与细胞内第二信使有关。     

乙酰胆碱对大鼠腹腔巨噬细胞内钙离子浓度和表面Ia抗原表达的影响

用Ｆｕｒａ－２作为荧光探针测定大鼠腹腔巨噬细胞（Ｍ）内钙离子浓度（［Ｃａ￣（２＋）］ｉ），ＡＰＡＡＰ桥联酶标法检测Ｍ表面Ｉａ抗原的表达。结果表明：５×１０￣（－６）ｍｏｌ／Ｌ的乙酞胆碱（Ａｃｈ）可使Ｍ［Ｃａ￣（２＋）］ｉ；明显上升，可促进Ｍ表面Ｉ－Ａ和Ｉ－Ｅ抗原的表达，而阿托品（１０￣（－５）ｍｏｌ／Ｌ）可阻断Ａｃｈ升高［Ｃａ￣（２＋）］ｉ的作用。阿托品、三氟啦嚎（ＴＦＰ，５０μｍｏｌ／Ｌ）、ＥＧＴＡ（６ｍｍｏｌ／Ｌ）均可阻断Ｍ促进ＭＩａ抗原表达的作用，ｃＡＭＰ依赖性蛋白激酶抑制剂（ＰＫＩ，２５μｇ／ｍｌ）对Ａｃｈ促进ＭＩａ抗原表达的作用无影响。     

Renal dysplasia and asplenia in two sibs

A family is reported in which two sibs, one male and the other female, both died within 24 hours of birth with enlarged polycystic kidneys. Postmortem histology in the second child showed gross renal dysplasia. In both children the pancreas was enlarged, nodular and cystic but the liver appeared macroscopically normal. In the second child, histological examination confirmed pancreatic fibrosis with cystic dilation of ducts, but showed portal fibrosis with bile duct proliferation in the liver.
This combination of findings is very reminiscent of those in a girl and her brother reported by Ivemark et al. (1959). The children reported here also showed absence or hypoplasia of the spleen, cardiac anomalies and other features of the Ivemark syndrome (Ivemark 1955), a quite different, usually sporadic, congenital disorder. It is suggested that the children described here have a distinct lethal congenital disorder, probably inherited in an autosomal recessive manner.     

Schizophrenia in a North Swedish geographical isolate, 1900–1977. Epidemiology, genetics and biochemistry

Over 200 schizophrenic patients belonging to three major and interrelated pedigree complexes have been investigated over the past 30 years in a North Swedish geographically isolated population, presently numbering about 6,000. An intensive investigation of a number of biochemical correlates and genetic markers in a few selected families belonging to one of the major pedigrees has indicated new strategies for the current research program.
Schizophrenia, as defined operationally, is significantly associated with decreased activities of two enzymes (1) blood platelet monoamine oxidase, (2) plasma dopamine-β-hydroxylase, and (3) with the genetic marker Gc² (group specific antigen). Both enzymes are subject to genetic variation. A positive score for linkage between schizophrenia and low plasma DBH activity has been calculated, but, so far, available data are insufficient for discrimination between linkage and partial contribution of genetically controlled low plasma DBH to the pathogenesis of the disease. Alternatively, both mechanisms could be involved.
As a model for continued research, schizophrenia is explained as based on a double dominant-recessive genotype (Aabb), representing a vulnerability which in about 50 % of cases develops into clinical schizophrenia. It is suggested that the dominant mutation (A) operates on or affects MAO activity, and that the recessive genotype (bb) is instrumental in low variates of DBH activity and very likely such variates within the normal range of physiological variation. Moreover, it is suggested that the combined effects of MAO- and DBH-reduced efficiency on the metabolism of e.g. dopamine could be an essential pathogenic mechanism for the schizophrenic illness which is segregating in this population.     

What will studies of Fulani individuals naturally exposed to malaria teach us about protective immunity to malaria?

There are an estimated over 200 million yearly cases of malaria worldwide. Despite concerted international effort to combat the disease, it still causes approximately half a million deaths every year, the majority of which are young children with Plasmodium falciparum infection in sub-Saharan Africa. Successes are largely attributed to malaria prevention strategies, such as insecticide-treated mosquito nets and indoor spraying, as well as improved access to existing treatments. One important hurdle to new approaches for the treatment and prevention of malaria is our limited understanding of the biology of Plasmodium infection and its complex interaction with the immune system of its human host. Therefore, the elimination of malaria in Africa not only relies on existing tools to reduce malaria burden, but also requires fundamental research to develop innovative approaches. Here, we summarize our discoveries from investigations of ethnic groups of West Africa who have different susceptibility to malaria.     

The dominant diseases of modernized societies as omega-3 essential fatty acid deficiency syndrome: Substrate beriberi

About 1900, modern food selection and processing caused widespread $\text{epidemics}$ of the B vitamin deficiency diseases of beriberi and pellagra which, for genetic reasons, often expressed as different diseases ranging from bowel and heart disease to dermatoses and psychoses. But the B vitamins merely help convert essential fatty acids (EFA) into the prostaglandin (PG) tissue regulators and it now turns out that, through hydrogenation, milling and selection of w3-poor southern foods, we have also been systematically depleting, by as much as 90%, a newly discovered trace Nordic EFA (w3) of special importance to primates and sole precursor of the PG3(4) series, even as a concurrent fiber deficiency increases body demand for EFA. Since substrate EFA is processed by many B vitamin catalysts, an EFA deficiency will mimic a $\text{panh}$ypovitaminosis B, i.e., a mixture of $\text{substrate}$ beriberi and $\text{substrate}$ pellagra resembling vitamin beriberi and pellagra but exhibiting as even more diverse $\text{endemic}$ disease. This would consitute a second stage of the Modern Malnutrition and explain why some workers now hold the dominant diseases of modermized societies to be new, nutritionally based, pellagraform yet lipid-related and to range, once again, from heart disease to psychosis. It is an assumption that our dominant diseases are unrelated to each other or are merely revealed by our diagnostic acumen and therapeutic success; and that hydrogenating millions of tons of food oils annually, to destroy the rancidity producing w3-EFA, is safe for $\text{primates}$. Extensive beriberiform disease is reported here in 32 typical cases taken from medical practice which responds strikingly to linseed oil supplements (60% w3-EFA) in confirmation of identical results in Capuchins.     

The universal muscular chain reaction,muscle spasm,Torsions, ruptures and extravasations. Chameleons of pathology and some manifestations of simple muscular disorders

Most bodily functions require the coordinated actions of complementary and supplementary paired muscle groups. Where this essential muscular cooperation is lacking, hollow organs may burst and others become literally screwed up, giving rise to many similar spastic diseases such as Torticollis, Twisted ovarian cyst, Torsion of the Testis, Volvulus of the intestines, Varicose Veins, Megacolon, Aortamegaly, Scoliosis, Erb's Palsy, Peyronie's Disease, Main-en-Griffe, Undescended Foot (Pes Cavus), Talipes, Strabismus. Spasm is “panenepidemic” and unclassified examples of Torsion Dystonia and Dyskinesia really are as common as debt and taxes.     

Class II HLA in Georgia Caucasus Tbilisi Georgians and their Mediterranean ancestry: The Usko Mediterranean languages

Georgia (or Sakartvelo in its own language) is a South Caucasus Mts. country with its easternmost part is enigmatically named Iberia, like the Iberian Peninsula, which may refer to rivers “Kura” and “Ebro” or their valleys respectively. Most of their inhabitants speak Georgian which is included within Dene-Caucasian group and Usko-Mediterranean subgroup of languages. The latter includes Basque, Berber, ancient Iberian-Tartessian, Etruscan, Hittite, Minoan Lineal A and others. In the present paper, HLA class II -DRB1 and -DQB1 alleles has been studied and extended haplotypes calculated. Most frequent haplotypes are also of Mediterranean origin (i. e.: (A*02-B*51)-DRB1*11:01-DQB1*03:01, (A*02-B*51)-DRB1*13:01-DQB1*06:03, or (A*24-B*35)-DRB1*01:01-DQB1*05:01) and DA genetic distances show that closest world populations to Georgians are Mediterraneans. Georgians also show common extended haplotypes ((A*02-B*51)-DRB1*11:01-DQB1*03:01, (A*02-B*13)-DRB1*07:01-DQB1*02:01 and (A*03-B*35)-DRB1*11:01-DQB1*03:01) with Svan people, a secluded population in North Georgia mountains. We can conclude that Georgians belong to a very old Mediterranean substratum according to both linguistics (Usko Mediterranean languages) and HLA genetics.     

'Very sore nights and days': the child's experience of illness in early modern England, c.1580-1720

Sick children were ubiquitous in early modern England, and yet they have received very little attention from historians. Taking the elusive perspective of the child, this article explores the physical, emotional, and spiritual experience of illness in England between approximately 1580 and 1720. What was it like being ill and suffering pain? How did the young respond emotionally to the anticipation of death? It is argued that children’s experiences were characterised by profound ambivalence: illness could be terrifying and distressing, but also a source of emotional and spiritual fulfilment and joy. This interpretation challenges the common assumption amongst medical historians that the experiences of early modern patients were utterly miserable. It also sheds light on children’s emotional feelings for their parents, a subject often overlooked in the historiography of childhood. The primary sources used in this article include diaries, autobiographies, letters, the biographies of pious children, printed possession cases, doctors’ casebooks, and theological treatises concerning the afterlife.     

Guidelines for the Validation and Use of Immunoassays for Determination of Introduced Proteins in Biotechnology Enhanced Crops and Derived Food Ingredients

Recent advancements in agricultural biotechnology have created a need for analytical techniques to determine introduced proteins in crops enhanced through modern biotechnology techniques. These proteins are expressed in plant tissues and may be present in food ingredients. Immunoassays are ideally suited for protein detection and may be used as both quantitative and threshold methods. Microplate ELISA and lateral flow devices are two of the most commonly used immunoassay formats for agricultural biotechnology applications. This paper provides general background information and a discussion of criteria for the validation and application of immunochemical methods to the analysis of proteins introduced into plants and food ingredients using biotechnology methods. It is the result of a collaborative effort of members of the Analytical Environmental Immunochemical Consortium. This collaborative effort represents the combined expertise of several organizations to reach consensus on establishing guidelines for the validation and use of immunoassays. Further, the paper offers developers and users a consistent approach to adopting the technology as well as aid in producing accurate and meaningful results.     

Ultracryotomy: development and application (with examples from the yeast cytology) (author's transl)

The preparation steps usually necessary for obtaining ultrathin frozen sections of biological material (chemical prefixation, enclosing, cryoprotective treatment, freezing, sectioning, and post-staining the sections for transmission electron microscopy) are submitted to a critical analysis. The application of cryo-ultramicrotomy, in particularly for cytochemical purposes, is reviewed. Fundamental considerations of chemical prefixation and poststaining are supported by examples from yeast cytology. Furthermore, the efficiency of the cryo-ultramicrotomy (electron optical resolution of ultrastructural details) is demonstrated on yeast cells and protoplasts.